The majority of our knowledge about the molecular mechanisms of cellular response to ionizing radiation exposure is based on experiments with traditional cell culture models. Of these models, cancer cell lines were used the most often, which may seem quite reasonable given that radiation therapy of cancers is the main clinical application of ionizing radiation in medicine. However, it is quite obvious that hESC, primary cell lines, established normal cell lines and established cancer cell lines have different responses to IR. Various primary cell lines obtained from different tissues, such as primary fibroblasts, are also often used in radiobiological studies. The results obtained from experiments using cultures of such terminally differentiated cells may not reflect the response to IR of a normal tissue that consists of various cell types, including progenitor and tissue stem cells. Because we now have a number of hESC lines approved for NIH Intramural experiments use by current ethical and regulatory requirements, I wish to sequentially use these genetically distinct hESC to determine by experimentation whether the patterns of gene activation following irradiation are truly common across these cell lines or whether each line will exhibit, in part at least, a distinct response to external and internal irradiations of various types and levels.